Bish, Lawrence T.Sleeper, Meg M.Brainard, BenjaminCole, StephenRussell, NicholasWithnall, ElanorArndt, JasonReynolds, CarynDavison, EllenSanmiguel, JulioWu, DiGao, GuangpingWilson, James M.Lee Sweeney, H2022-08-232022-08-232008-12-012017-05-17Mol Ther. 2008 Dec;16(12):1953-1959. doi: 10.1038/mt.2008.202. Epub 2016 Dec 8. <a href="https://doi.org/10.1038/mt.2008.202">Link to article on publisher's site</a>1525-0016 (Linking)10.1038/mt.2008.20228189009https://hdl.handle.net/20.500.14038/40244Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated-ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6-so that comparison could be made between single-stranded and self-complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15-4,000 times more abundant in the heart than in any other organ for scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective method to achieve efficient cardiac gene transfer.en-UShttp://creativecommons.org/licenses/by-nc-nd/4.0/CardiologyCellular and Molecular PhysiologyGenetics and GenomicsTherapeuticsJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4043&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/303810176542oapubs/3038